Cardiac calcium release channel (ryanodine receptor) in control and cardiomyopathic human hearts: MRNA and protein contents are differentially regulated

C. Sainte Beuve, P. D. Allen, G. Dambrin, F. Rannou, I. Marty, P. Trouvé, V. Bors, A. Pavie, I. Gandgjbakch, D. Charlemagne

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Abnormal intracellular calcium handling in cardiomyopathic human hearts has been associated with an impaired function of the sarcoplasmic reticulum, but previous reports on the gene expression of the ryanodine receptors (Ry2) are contradictory. We measured the mRNA levels, the protein levels and the number of high affinity [3H] ryanodine binding sites in the left ventricle of non-failing (n = 9) and failing human hearts [idiopathic dilated (IDCM n = 16), ischemic (ICM n = 7) or mixed (MCM n = 8) cardiomyopathies]. Ry2 mRNA levels were significantly reduced in IDCM (-30%) and unchanged in MCM and ICM and Ry2 protein levels were similar, In contrast, we observed a two-fold increase in the number of high affinity Ry2 (B(max) = 0.43 ± 0.11 v 0.22 ± 0.13 pmol/mg protein, respectively; P<0.01) and an unchanged K(d). Furthermore, levels of myosin heavy chain mRNA and protein per g of tissue were similar in failing and non-failing hearts, suggesting that the observed differences in Ry2 are not caused by the increase in fibrosis in failing heart. Therefore, the dissociation between the two-fold increase in the number of high affinity ryanodine receptors observed in all failing hearts and the slightly decreased mRNA level or unchanged protein level suggests that the ryanodine binding properties are affected in failing myocardium and that such modifications rather than a change in gene expression alter the channel activity and could contribute to abnormalities in intracellular Ca2+ handling.

Original languageEnglish (US)
Pages (from-to)1237-1246
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume29
Issue number4
DOIs
StatePublished - Apr 1997
Externally publishedYes

Keywords

  • [H]ryanodine binding
  • mRNA
  • Ryanodine receptors
  • Western blot

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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    Sainte Beuve, C., Allen, P. D., Dambrin, G., Rannou, F., Marty, I., Trouvé, P., Bors, V., Pavie, A., Gandgjbakch, I., & Charlemagne, D. (1997). Cardiac calcium release channel (ryanodine receptor) in control and cardiomyopathic human hearts: MRNA and protein contents are differentially regulated. Journal of Molecular and Cellular Cardiology, 29(4), 1237-1246. https://doi.org/10.1006/jmcc.1996.0360